The use of taxanes, such as paclitaxel, as anti-tumor agents for patients suffering from diseases, such as ovarian and breast cancer, is known. In addition, paclitaxel has been shown to be clinically potent as a synergistic agent when used in conjunction with radiation treatment. Paclitaxel has a unique mechanism of action and a broad spectrum of anticancer activity because paclitaxel shows stabilization of microtubules rather than disassembly of microtubules.
However, paclitaxel has extremely low solubility in water, which makes it difficult to provide a suitable dosage form. Currently, paclitaxel is prepared and administered in a vehicle containing 6 mg/mL paclitaxel, 527 mg/mL of purified cremophor EL (a polyethoxylated castor oil), and 49.7% dehydrated alcohol, USP. This solution is diluted 1:10 in saline before being administered to humans. The stability of paclitaxel once diluted in saline solution is quite low. The drug degrades within 24 hours, and it has been shown that taxol is incompatible with common PVC intravenous bag and infusion sets, thus, handling of dosage for the patients becomes very difficult. Since the drug precipitates from dilution, an on-line filter is utilized for the infusion of the drug to the patients. The decreased solubility and presence of Cremophor EL in the formulations presents risks to patients, such as anaphylactoid reactions and cardiotoxicity. The long-term use of taxol also can contribute to the development of multidrug resistence in cancer cells, which only complicates the etiology of the very disease for which taxol treatment is sought.
Attempts have been made to improve upon the currently-available formulations of taxol. To this end, U.S. Pat. No. 5,648,090 (Rahman et al.) and U.S. Pat. No. 5,424,073 (Rahman et al.) provide a liposomal encapsulated paclitaxel for a method for treating cancer in mammals using such a liposomal-encapsulated paclitaxel, or antineoplastic derivative thereof. The '090 and '073 patents disclose a method of modulating multidrug resistance in cancer cells in a mammalian host by administering to the host a pharmaceutical composition of a therapeutically effective number of liposomes, which include a liposome-forming material, cardiolipin, and an agent such as paclitaxel, or an antineoplastic derivative of paclitaxel, or a mixture thereof, and a pharmaceutically acceptable excipient. However, there remains a need for a liposomal formulation of taxanes that remain stable for a prolonged period of time.